The ageing epigenome and its rejuvenation Zhang, Weiqi; Qu, Jing; Liu, Guang-Hui ...
Nature reviews. Molecular cell biology,
03/2020, Letnik:
21, Številka:
3
Journal Article
Recenzirano
Ageing is characterized by the functional decline of tissues and organs and the increased risk of ageing-associated disorders. Several 'rejuvenating' interventions have been proposed to delay ageing ...and the onset of age-associated decline and disease to extend healthspan and lifespan. These interventions include metabolic manipulation, partial reprogramming, heterochronic parabiosis, pharmaceutical administration and senescent cell ablation. As the ageing process is associated with altered epigenetic mechanisms of gene regulation, such as DNA methylation, histone modification and chromatin remodelling, and non-coding RNAs, the manipulation of these mechanisms is central to the effectiveness of age-delaying interventions. This Review discusses the epigenetic changes that occur during ageing and the rapidly increasing knowledge of how these epigenetic mechanisms have an effect on healthspan and lifespan extension, and outlines questions to guide future research on interventions to rejuvenate the epigenome and delay ageing processes.
In order to analyze the reform effect of individual income tax policy in 2018, the income redistribution effect of various individual income tax collection schemes is compared through the tracking ...survey data of China Family Panel Studies. The research shows that the personal income tax reform has reduced the tax burden of taxpayers on the whole. Among the four reform measures, only the implementation of comprehensive income tax has a positive effect on the distribution effect. As the main beneficiaries are mainly high-income people, this round of reform has weakened the redistribution effect on residents’ income. Therefore, measures such as adhering to the direction of comprehensive taxation, prudently reforming the basic reduction of fees and tax rates, subsidizing low-income people and strengthening the supervision of high-income people will help to enhance the redistribution effect of individual income tax.
Spinal cord injury (SCI) represents one of the most complicated and heterogeneous pathological processes of central nervous system (CNS) impairments, which is still beyond functional regeneration. ...Transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of the injured spinal cord tissues in animal models, and therefore, there is much interest in the clinical use of these cells. However, many questions which are essential to improve the therapy effects remain unanswered. For instance, the functional roles and related molecular regulatory mechanisms of MSCs in vivo are not yet completely determined. It is important for transplanted cells to migrate into the injured tissue, to survive and undergo neural differentiation, or to play neural protection roles by various mechanisms after SCI. In this review, we will focus on some of the recent knowledge about the biological behavior and function of MSCs in SCI. Meanwhile, we highlight the function of biomaterials to direct the behavior of MSCs based on our series of work on silk fibroin biomaterials and attempt to emphasize combinational strategies such as tissue engineering for functional improvement of SCI.
Background
The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2, also called 2019-nCoV) recently break out in Wuhan, China, and was named as COVID-19. With the spread of the disease, ...similar cases have also been confirmed in other regions of China. We aimed to report the imaging and clinical characteristics of these patients infected with SARS-CoV-2 in Guangzhou, China.
Methods
All patients with laboratory-identified SARS-CoV-2 infection by real-time polymerase chain reaction (PCR) were collected between January 23, 2020, and February 4, 2020, in a designated hospital (Guangzhou Eighth People’s Hospital). This analysis included 90 patients (39 men and 51 women; median age, 50 years (age range, 18–86 years). All the included SARS-CoV-2-infected patients underwent non-contrast enhanced chest computed tomography (CT). We analyzed the clinical characteristics of the patients, as well as the distribution characteristics, pattern, morphology, and accompanying manifestations of lung lesions. In addition, after 1–6 days (mean 3.5 days), follow-up chest CT images were evaluated to assess radiological evolution.
Findings
The majority of infected patients had a history of exposure in Wuhan or to infected patients and mostly presented with fever and cough. More than half of the patients presented bilateral, multifocal lung lesions, with peripheral distribution, and 53 (59%) patients had more than two lobes involved. Of all included patients, COVID-19 pneumonia presented with ground glass opacities in 65 (72%), consolidation in 12 (13%), crazy paving pattern in 11 (12%), interlobular thickening in 33 (37%), adjacent pleura thickening in 50 (56%), and linear opacities combined in 55 (61%). Pleural effusion, pericardial effusion, and lymphadenopathy were uncommon findings. In addition, baseline chest CT did not show any abnormalities in 21 patients (23%), but 3 patients presented bilateral ground glass opacities on the second CT after 3–4 days.
Conclusion
SARS-CoV-2 infection can be confirmed based on the patient’s history, clinical manifestations, imaging characteristics, and laboratory tests. Chest CT examination plays an important role in the initial diagnosis of the novel coronavirus pneumonia. Multiple patchy ground glass opacities in bilateral multiple lobular with periphery distribution are typical chest CT imaging features of the COVID-19 pneumonia.
Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates ...(NHPs) and identified seven ovarian cell types with distinct gene-expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene-expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell-type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis were observed in granulosa cells from aged women. This study provides a comprehensive understanding of the cell-type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.
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•Single-cell transcriptomic roadmap of NHP ovarian aging•Molecular signatures revealed for NHP oocytes at stepwise developmental stages•Cell-type-specific inactivation of antioxidant genes in aged monkey and human ovaries
Single-cell transcriptomic analysis in ovaries of young and old cynomolgus monkeys identifies aging-associated and cell-type-specific dysregulation of antioxidative pathways.
Our understanding of how aging affects the cellular and molecular components of the vasculature and contributes to cardiovascular diseases is still limited. Here we report a single-cell ...transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. Our data define the molecular signatures of specialized arteries and identify eight markers discriminating aortic and coronary vasculatures. Gene network analyses characterize transcriptional landmarks that regulate vascular senility and position FOXO3A, a longevity-associated transcription factor, as a master regulator gene that is downregulated in six subtypes of monkey vascular cells during aging. Targeted inactivation of FOXO3A in human vascular endothelial cells recapitulates the major phenotypic defects observed in aged monkey arteries, verifying FOXO3A loss as a key driver for arterial endothelial aging. Our study provides a critical resource for understanding the principles underlying primate arterial aging and contributes important clues to future treatment of age-associated vascular disorders.
Metallic nanoparticles (MNPs) are new engineering materials with broad prospects for biomedical applications; thus, their biosafety has drawn great concern. The liver is the main detoxification organ ...of vertebrates. However, many issues concerning the interactions between MNPs and biological systems (cells and tissues) are unclear, particularly the toxic effects of MNPs on hepatocytes and other liver cells. Numerous researchers have shown that some MNPs can induce decreased cell survival rate, production of reactive oxygen species (ROS), mitochondrial damage, DNA strand breaks, and even autophagy, pyroptosis, apoptosis, or other forms of cell death. Our review focuses on the recent researches on the liver toxicity of MNPs and its mechanisms at cellular and subcellular levels to provide a scientific basis for the subsequent hepatotoxicity studies of MNPs.
Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular ...and molecular mechanisms associated with aging in higher mammals is therefore urgently needed. Here, we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart and artery, the top tissues targeted by SARS-CoV-2. Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging. With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression. Altogether, our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare, invariably fatal premature aging disorder. The disease is caused by constitutive production of progerin, a mutant form of the nuclear ...architectural protein lamin A, leading, through unknown mechanisms, to diverse morphological, epigenetic, and genomic damage and to mesenchymal stem cell (MSC) attrition in vivo. Using a high-throughput siRNA screen, we identify the NRF2 antioxidant pathway as a driver mechanism in HGPS. Progerin sequesters NRF2 and thereby causes its subnuclear mislocalization, resulting in impaired NRF2 transcriptional activity and consequently increased chronic oxidative stress. Suppressed NRF2 activity or increased oxidative stress is sufficient to recapitulate HGPS aging defects, whereas reactivation of NRF2 activity in HGPS patient cells reverses progerin-associated nuclear aging defects and restores in vivo viability of MSCs in an animal model. These findings identify repression of the NRF2-mediated antioxidative response as a key contributor to the premature aging phenotype.
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•Impaired activity of the NRF2 antioxidative pathway is a driver mechanism in HGPS•Suppressed NRF2 activity and oxidative stress recapitulate HGPS aging defects•Reactivation of NRF2 decreases oxidative stress and reverses cellular HGPS defects
Impairment of the NRF2 pathway is a key contributor to premature aging in Hutchinson-Gilford progeria syndrome (HGPS) via increasing chronic oxidative stress that recapitulates HGPS aging defects.
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